tbuckley/cabot-search huggingface dataset:
The Broader Economic Value of Treatment for Diabetic Macular Edema
Authors: Karen Mulligan, Jaehong Kim, Bryan Tysinger, Jill Blim, Geoffrey Emerson, Philip J. Ferrone, Judy E. Kim, Seth Seabury, Paul Hahn
Journal: Diabetes Care (2023)

OBJECTIVE To simulate economic outcomes for individuals with diabetic macular edema (DME) and estimate the economic value of direct and indirect benefits associated with DME treatment. RESEARCH DESIGN AND METHODS Our study pairs individual and cohort analyses to demonstrate the value of treatment for DME. We used a microsimulation model to simulate self-reported vision (SRV) and economic outcomes for individuals with DME. Four scenarios derived from clinical trial data were simulated and compared for a lifetime horizon: untreated, anti-VEGF therapy, laser, and steroid. To quantify the relative magnitude of costs and benefits of DME treatment in the U.S., we used a cohort-level analysis based on real-world treatment parameters derived from published data. RESULTS In the model, excellent/good SRV roughly corresponded to 20/40 or better visual acuity. A representative 51-year-old treated for DME would spend 30–35% additional years with excellent/good SRV and 29–32% fewer years with fair/poor SRV relative to being untreated. A treated individual would experience 4–5% greater life expectancy and 9–13% more quality-adjusted life-years. Indirect benefits from treatment included 6–9% more years working, 12–19% greater lifetime earnings, and 8–16% fewer years with disability. For the U.S. DME cohort (1.1. million people), total direct benefit was $63.0 billion over 20 years, and total indirect benefit was $4.8 billion. Net value (benefit − cost) of treatment ranged from $28.1 billion to $52.8 billion. CONCLUSIONS Treatment for DME provides economic value to patients and society through improved vision, life expectancy, and quality of life and indirectly through improved employment and disability outcomes.
Versatile Microfluidics for Biofabrication Platforms Enabled by an Agile and Inexpensive Fabrication Pipeline
Authors: Amirpasha Moetazedian, Alessia Candeo, Siyun Liu, Arran Hughes, Vahid Nasrollahi, Mozafar Saadat, Andrea Bassi, Liam M. Grover, Liam R. Cox, Gowsihan Poologasundarampillai
Journal: Advanced Healthcare Materials (2023)

Microfluidics have transformed diagnosis and screening in regenerative medicine. Recently, they are showing much promise in biofabrication. However, their adoption is inhibited by costly and drawn-out lithographic processes thus limiting progress. Here, multi-material fibers with complex core-shell geometries with sizes matching those of human arteries and arterioles are fabricated employing versatile microfluidic devices produced using an agile and inexpensive manufacturing pipeline. The pipeline consists of material extrusion additive manufacturing with an innovative continuously varied extrusion (CONVEX) approach to produce microfluidics with complex seamless geometries including, novel variable-width zigzag (V-zigzag) mixers with channel widths ranging from 100-400 µm and hydrodynamic flow-focusing components. The microfluidic systems facilitated rapid mixing of fluids by decelerating the fluids at specific zones to allow for increased diffusion across the interfaces. Better mixing even at high flow rates (100-1000 µL min
A metabolic perspective of selection for fruit quality related to apple domestication and improvement
Authors: Qiong Lin, Jing Chen, Xuan Liu, Bin Wang, Yaoyao Zhao, Liao Liao, Andrew C. Allan, Chongde Sun, Yuquan Duan, Xuan Li, Donald Grierson, Julian C. Verdonk, Kunsong Chen, Yuepeng Han, Jinfeng Bi
Journal: Genome biology (2023)

Apple is an economically important fruit crop. Changes in metabolism accompanying human-guided evolution can be revealed using a multiomics approach. We perform genome-wide metabolic analysis of apple fruits collected from 292 wild and cultivated accessions representing various consumption types.We find decreased amounts of certain metabolites, including tannins, organic acids, phenolic acids, and flavonoids as the wild accessions transition to cultivated apples, while lysolipids increase in the "Golden Delicious" to "Ralls Janet" pedigree, suggesting better storage. We identify a total of 222,877 significant single-nucleotide polymorphisms that are associated with 2205 apple metabolites. Investigation of a region from 2.84 to 5.01 Mb on chromosome 16 containing co-mapping regions for tannins, organic acids, phenolic acids, and flavonoids indicates the importance of these metabolites for fruit quality and nutrition during breeding. The tannin and acidity-related genes Myb9-like and PH4 are mapped closely to fruit weight locus fw1 from 3.41 to 3.76 Mb on chromosome 15, a region under selection during domestication. Lysophosphatidylethanolamine (LPE) 18:1, which is suppressed by fatty acid desaturase-2 (FAD2), is positively correlated to fruit firmness. We find the fruit weight is negatively correlated with salicylic acid and abscisic acid levels. Further functional assays demonstrate regulation of these hormone levels by NAC-like activated by Apetala3/Pistillata (NAP) and ATP binding cassette G25 (ABCG25), respectively.This study provides a metabolic perspective for selection on fruit quality during domestication and improvement, which is a valuable resource for investigating mechanisms controlling apple metabolite content and quality.
Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2–, PIK3CA-mutated breast cancers
Authors: Katherine E. Hutchinson, Jessica W. Chen, Heidi M. Savage, Thomas J. Stout, Frauke Schimmoller, Javier Cortés, Susan Dent, Nadia Harbeck, William Jacot, Ian Krop, Sally E. Trabucco, Smruthy Sivakumar, Ethan S. Sokol, Timothy R. Wilson
Journal: Genome Medicine (2023)

Abstract Background Mutations in the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), encoded by the PIK3CA gene, cause dysregulation of the PI3K pathway in 35–40% of patients with HR+/HER2– breast cancer. Preclinically, cancer cells harboring double or multiple PIK3CA mutations (mut) elicit hyperactivation of the PI3K pathway leading to enhanced sensitivity to p110α inhibitors. Methods To understand the role of multiple PIK3CA mut in predicting response to p110α inhibition, we estimated the clonality of multiple PIK3CA mut in circulating tumor DNA (ctDNA) from patients with HR+/HER2– metastatic breast cancer enrolled to a prospectively registered clinical trial of fulvestrant ± taselisib, and analyzed the subgroups against co-altered genes, pathways, and outcomes. Results ctDNA samples with clonal multiple PIK3CA mut had fewer co-alterations in receptor tyrosine kinase (RTK) or non- PIK3CA PI3K pathway genes compared to samples with subclonal multiple PIK3CA mut indicating a strong reliance on the PI3K pathway. This was validated in an independent cohort of breast cancer tumor specimens that underwent comprehensive genomic profiling. Furthermore, patients whose ctDNA harbored clonal multiple PIK3CA mut exhibited a significantly higher response rate and longer progression-free survival vs subclonal multiple PIK3CA mut. Conclusions Our study establishes clonal multiple PIK3CA mut as an important molecular determinant of response to p110α inhibition and provides rationale for further clinical investigation of p110α inhibitors alone or with rationally-selected therapies in breast cancer and potentially other solid tumor types.
Role of pyroptosis in the pathogenesis and treatment of diseases
Authors: Xiangyu Jin, Yinchu Ma, Didi Liu, Yi Huang
Journal: MedComm (2023)

Abstract Programmed cell death (PCD) is regarded as a pathological form of cell death with an intracellular program mediated, which plays a pivotal role in maintaining homeostasis and embryonic development. Pyroptosis is a new paradigm of PCD, which has received increasing attention due to its close association with immunity and disease. Pyroptosis is a form of inflammatory cell death mediated by gasdermin that promotes the release of proinflammatory cytokines and contents induced by inflammasome activation. Recently, increasing evidence in studies shows that pyroptosis has a crucial role in inflammatory conditions like cardiovascular diseases (CVDs), cancer, neurological diseases (NDs), and metabolic diseases (MDs), suggesting that targeting cell death is a potential intervention for the treatment of these inflammatory diseases. Based on this, the review aims to identify the molecular mechanisms and signaling pathways related to pyroptosis activation and summarizes the current insights into the complicated relationship between pyroptosis and multiple human inflammatory diseases (CVDs, cancer, NDs, and MDs). We also discuss a promising novel strategy and method for treating these inflammatory diseases by targeting pyroptosis and focus on the pyroptosis pathway application in clinics.
Diverse but desolate landscape of gut microbial azoreductases: A rationale for idiopathic IBD drug response
Authors: Joshua B. Simpson, Josh J. Sekela, Benjamin S. Carry, Violet Beaty, Shakshi Patel, Matthew. R. Redinbo
Journal: Gut Microbes (2023)

Prodrugs reliant on microbial activation are widely used but exhibit a range of efficacies that remain poorly understood. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA), which is packaged in a variety of azo-linked prodrugs provided to most Ulcerative Colitis (UC) patients, shows confounding inter-individual variabilities in response. Such prodrugs must be activated by azo-bond reduction to form 5-ASA, a process that has been attributed to both enzymatic and non-enzymatic catalysis. Gut microbial azoreductases (AzoRs) are the first catalysts shown to activate azo-linked drugs and to metabolize toxic azo-chemicals. Here, we chart the scope of the structural and functional diversity of AzoRs in health and in patients with the inflammatory bowel diseases (IBDs) UC and Crohn's Disease (CD). Using structural metagenomics, we define the landscape of gut microbial AzoRs in 413 healthy donor and 1059 IBD patient fecal samples. Firmicutes encode a significantly higher number of unique AzoRs compared to other phyla. However, structural and biochemical analyses of distinct AzoRs from the human microbiome reveal significant differences between prevalent orthologs in the processing of toxic azo-dyes, and their generally poor activation of IBD prodrugs. Furthermore, while individuals with IBD show higher abundances of AzoR-encoding gut microbial taxa than healthy controls, the overall abundance of AzoR-encoding microbes is markedly low in both disease and health. Together, these results establish that gut microbial AzoRs are functionally diverse but sparse in both health and disease, factors that may contribute to non-optimal processing of azo-linked prodrugs and idiopathic IBD drug responses.
Assessing nocturnal scratch with actigraphy in atopic dermatitis patients
Authors: Ju Ji, Jordan Venderley, Hui Zhang, Mengjue Lei, Guangchen Ruan, Neel Patel, Yu-Min Chung, Regan Giesting, Leah Miller
Journal: npj Digital Medicine (2023)

Abstract Nocturnal scratch is one major factor leading to impaired quality of life in atopic dermatitis (AD) patients. Therefore, objectively quantifying nocturnal scratch events aids in assessing the disease state, treatment effect, and AD patients’ quality of life. In this paper, we describe the use of actigraphy, highly predictive topological features, and a model-ensembling approach to develop an assessment of nocturnal scratch events by measuring scratch duration and intensity. Our assessment is tested in a clinical setting against the ground truth obtained from video recordings. The new approach addresses unmet challenges in existing studies, such as the lack of generalizability to real-world applications, the failure to capture finger scratches, and the limitations in the evaluation due to imbalanced data in the current literature. Furthermore, the performance evaluation shows agreement between derived digital endpoints and the video annotation ground truth, as well as patient-reported outcomes, which demonstrated the validity of the new assessment of nocturnal scratch.
A comprehensive map of human glucokinase variant activity
Authors: Sarah Gersing, Matteo Cagiada, Marinella Gebbia, Anette P. Gjesing, Atina G. Coté, Gireesh Seesankar, Roujia Li, Daniel Tabet, Jochen Weile, Amelie Stein, Anna L. Gloyn, Torben Hansen, Frederick P. Roth, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Journal: Genome biology (2023)

Abstract Background Glucokinase (GCK) regulates insulin secretion to maintain appropriate blood glucose levels. Sequence variants can alter GCK activity to cause hyperinsulinemic hypoglycemia or hyperglycemia associated with GCK-maturity-onset diabetes of the young (GCK-MODY), collectively affecting up to 10 million people worldwide. Patients with GCK-MODY are frequently misdiagnosed and treated unnecessarily. Genetic testing can prevent this but is hampered by the challenge of interpreting novel missense variants. Result Here, we exploit a multiplexed yeast complementation assay to measure both hyper- and hypoactive GCK variation, capturing 97% of all possible missense and nonsense variants. Activity scores correlate with in vitro catalytic efficiency, fasting glucose levels in carriers of GCK variants and with evolutionary conservation. Hypoactive variants are concentrated at buried positions, near the active site, and at a region of known importance for GCK conformational dynamics. Some hyperactive variants shift the conformational equilibrium towards the active state through a relative destabilization of the inactive conformation. Conclusion Our comprehensive assessment of GCK variant activity promises to facilitate variant interpretation and diagnosis, expand our mechanistic understanding of hyperactive variants, and inform development of therapeutics targeting GCK.
Self-supervised learning for medical image classification: a systematic review and implementation guidelines
Authors: Shih-Cheng Huang, Anuj Pareek, Malte Jensen, Matthew P. Lungren, Serena Yeung, Akshay S. Chaudhari
Journal: npj Digital Medicine (2023)

Advancements in deep learning and computer vision provide promising solutions for medical image analysis, potentially improving healthcare and patient outcomes. However, the prevailing paradigm of training deep learning models requires large quantities of labeled training data, which is both time-consuming and cost-prohibitive to curate for medical images. Self-supervised learning has the potential to make significant contributions to the development of robust medical imaging models through its ability to learn useful insights from copious medical datasets without labels. In this review, we provide consistent descriptions of different self-supervised learning strategies and compose a systematic review of papers published between 2012 and 2022 on PubMed, Scopus, and ArXiv that applied self-supervised learning to medical imaging classification. We screened a total of 412 relevant studies and included 79 papers for data extraction and analysis. With this comprehensive effort, we synthesize the collective knowledge of prior work and provide implementation guidelines for future researchers interested in applying self-supervised learning to their development of medical imaging classification models.
Ribavirin treatment for respiratory syncytial virus infection in patients with haematologic malignancy and haematopoietic stem cell transplant recipients: a systematic review and meta-analysis
Authors: Kasama Manothummetha, Thanuthong Mongkolkaew, Punyot Tovichayathamrong, Rabhas Boonyawairote, Tanaporn Meejun, Karan Srisurapanont, Kasidis Phongkhun, Anawin Sanguankeo, Pattama Torvorapanit, Chatphatai Moonla, Rongpong Plongla, Olivia S. Kates, Robin K. Avery, Saman Nematollahi, Nitipong Permpalung
Journal: Clinical Microbiology and Infection (2023)
Circular MTHFD2L RNA-encoded CM-248aa inhibits gastric cancer progression by targeting the SET-PP2A interaction
Authors: Haohan Liu, Deliang Fang, Chaoyue Zhang, Zirui Zhao, Yinan Liu, Shaoji Zhao, Nu Zhang, Jianbo Xu
Journal: Molecular Therapy (2023)

The available targeted therapies for gastric cancer (GC) are still limited, so it is important to discover novel molecules as potential treatment options. Proteins or peptides encoded by circular RNAs (circRNAs) are increasingly reported to play essential roles in malignancies. The aim of the present study was to identify an undiscovered protein encoded by circRNA and explore its key role and molecular mechanism in GC progression. CircMTHFD2L (hsa_circ_0069982) was screened and validated as a downregulated circRNA with coding potential. The protein encoded by circMTHFD2L, named CM-248aa, was identified for the first time by immunoprecipitation and mass spectrometry. CM-248aa was significantly downregulated in GC, while its low expression was associated with advanced tumor-node-metastasis (TNM) stage and histopathological grade. Low expression of CM-248aa could be an independent risk factor for poor prognosis. Functionally, CM-248aa, instead of circMTHFD2L suppressed the proliferation and metastasis of GC in vitro and in vivo. Mechanistically, CM-248aa competitively targeted the acidic domain of SET nuclear oncogene (SET) and acted as an endogenous inhibitor of the SET-protein phosphatase 2A interaction to promote dephosphorylation of AKT, extracellular signal-regulated kinase, and P65. Our discovery revealed that CM-248aa could be a potential prognostic biomarker and endogenous therapeutic option for GC.
Origin and Heterogeneity of Tissue Myeloid Cells: A Focus on GMP-Derived Monocytes and Neutrophils
Authors: Lai Guan Ng, Zhaoyuan Liu, Immanuel Kwok, Florent Ginhoux
Journal: Annual Review of Immunology (2023)

Myeloid cells are a significant proportion of leukocytes within tissues, comprising granulocytes, monocytes, dendritic cells, and macrophages. With the identification of various myeloid cells that perform separate but complementary functions during homeostasis and disease, our understanding of tissue myeloid cells has evolved significantly. Exciting findings from transcriptomics profiling and fate-mapping mouse models have facilitated the identification of their developmental origins, maturation, and tissue-specific specializations. This review highlights the current understanding of tissue myeloid cells and the contributing factors of functional heterogeneity to better comprehend the complex and dynamic immune interactions within the healthy or inflamed tissue. Specifically, we discuss the new understanding of the contributions of granulocyte-monocyte progenitor–derived phagocytes to tissue myeloid cell heterogeneity as well as the impact of niche-specific factors on monocyte and neutrophil phenotype and function. Lastly, we explore the developing paradigm of myeloid cell heterogeneity during inflammation and disease.
Engineering of an Osteoinductive and Growth Factor‐Free Injectable Bone‐Like Microgel for Bone Regeneration (Adv. Healthcare Mater. 11/2023)
Authors: Ramesh Subbiah, Edith Y. Lin, Avathamsa Athirasala, Genevieve E. Romanowicz, Angela S. P. Lin, Joseph V. Califano, Robert E. Guldberg, Luiz E. Bertassoni
Journal: Advanced Healthcare Materials (2023)

Biomineralization Article 2200976 by Luiz E. Bertassoni and co-workers presents injectable cell-laden bone-like tissue constructs that show promise as minimally invasive and growth factor-free alternatives to bone autografts for repair and regeneration of critical sized bone defects. By approximating the cellular, structural, and chemical composition of native bone, the engineered microconstructs promote native-like mechanisms of osteogenesis via unique mechanotransductive and phosphate signaling pathways.
Long-term treatment outcomes and safety of dupilumab as a therapy for bullous pemphigoid: A multicenter retrospective review
Authors: Christine Learned, Stephanie R. Cohen, Kaitlynne Cunningham, Sarah Alsukait, Sueheidi Santiago, Jun Lu, Marti Rothe, Anna Nichols, David Rosmarin
Journal: Journal of the American Academy of Dermatology (2023)
Novel Titanium Implant: A 3D Multifunction Architecture with Charge‐Trapping and Piezoelectric Self‐Stimulation (Adv. Healthcare Mater. 11/2023)
Authors: Lei Sun, Xuzhuo Chen, Kun Ma, Ruiguo Chen, Yi Mao, Rui Chao, Hui Wang, Bin Yu, Junfeng Wang, Shanyong Zhang
Journal: Advanced Healthcare Materials (2023)
Suppression of Lung Cancer Malignancy by Micellized siRNA through Cell Cycle Arrest (Adv. Healthcare Mater. 11/2023)
Authors: Haejoo Kim, In‐ho Jeong, Yeol Kyo Choi, Yeon Kyung Lee, Eunyoung Moon, Yang Hoon Huh, Wonpil Im, Jun‐O Jin, Minseok Kwak, Peter Chang‐Whan Lee
Journal: Advanced Healthcare Materials (2023)

Gene Therapy In article 2202358, Minseok Kwak, Peter Chang-Whan Lee, and co-workers show effective tumor suppression using RNAi with just three DNA and RNA strands. This transfection reagent-free technique self-assembles siRNAs and covers DNA micelles to create nanomedicine for lung cancer. Raw data files are used to create a montage background, recognizing the work of graduate students.
Sample size calculations for pathogen variant surveillance in the presence of biological and systematic biases
Authors: Shirlee Wohl, Elizabeth C. Lee, Bethany L. DiPrete, Justin Lessler
Journal: Cell Reports Medicine (2023)

Tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. To that end, accurately estimating the number and prevalence of pathogen variants in a population requires carefully designed surveillance programs. However, current approaches to calculating the number of pathogen samples needed for effective surveillance often do not account for the various processes that can bias which infections are detected and which samples are ultimately characterized as a specific variant. In this article, we introduce a framework that accounts for the logistical and epidemiological processes that may bias variant characterization, and we demonstrate how to use this framework (implemented in a publicly available tool) to calculate the number of sequences needed for surveillance. Our framework is designed to be easy to use while also flexible enough to be adapted to various pathogens and surveillance scenarios.
Transcriptomic Changes toward Osteogenic Differentiation of Mesenchymal Stem Cells on 3D‐Printed GelMA/CNC Hydrogel under Pulsatile Pressure Environment (Adv. Healthcare Mater. 11/2023)
Authors: Keya Ganguly, Sayan Deb Dutta, Aayushi Randhawa, Dinesh K. Patel, Tejal V. Patil, Ki‐Taek Lim
Journal: Advanced Healthcare Materials (2023)

Osteogenesis Pulsatile pressure assists early osteogenesis evaluation onto a 3D-printed soft hydrogel. Article 2202163 by Ki-Taek Lim and co-workers demonstrates the use of short-term pressure stimulation and its effect on proliferation, radical scavenging, and osteogenesis of stem cells. The results highlight the transcriptomic changes in stem cells toward bone regeneration.
Silk‐in‐Silk Nerve Guidance Conduits Enhance Regeneration in a Rat Sciatic Nerve Injury Model (Adv. Healthcare Mater. 11/2023)
Authors: Lorenz Semmler, Aida Naghilou, Flavia Millesi, Sonja Wolf, Anda Mann, Sarah Stadlmayr, Sascha Mero, Leon Ploszczanski, Lisa Greutter, Adelheid Woehrer, Eva Placheta‐Györi, Fritz Vollrath, Tamara Weiss, Christine Radtke
Journal: Advanced Healthcare Materials (2023)

Silk Fibers Silk has emerged as a versatile biomaterial for regenerative medicine. In article 2203237, Christine Radtke and co-workers use a silk-based nerve conduit filled with spider silk fibers to treat a rat sciatic nerve defect. The silk-in-silk conduit achieves a similar regenerative performance as the current gold standard, the autograft, and represents a promising approach for nerve reconstruction.